The University of Osaka · 신경과학
마사유키 나카모리 교수의 연구실은 육상 근육에서의 전사형 변이와 유전자 발현 조절 메커니즘을 중심으로, 미오토닉 약화증(MD1/DM2)을 비롯한 신경근육계 퇴행성 질환의 병태생리학을 규명하고 있습니다. 특히, CTG/CAG 반복 반복 서열의 유전자 안정성과 전사에 의한 변동성, IL-6 신호 경로 및 도르프린 단백질의 이소형 전사 조절 이상이 질병 진행에 미치는 영향을 집중적으로 연구하고 있습니다. 또한, 약물 치료 전략으로서 에리스로마이신의 임상적 잠재성에 대해서도 기초적 연구를 수행하고 있습니다.
표시된 성과는 수집된 데이터 기준으로 산출되며, 일부 차이가 있을 수 있습니다.
Alternative splicing changes in skeletal muscle may serve as biomarkers of disease severity and therapeutic response in myotonic dystrophy.
More than 12 neurogenetic disorders are caused by unstable expansions of (CTG)•(CAG) repeats. The expanded repeats are unstable in germline and somatic cells, with potential consequences for disease severity. Previous studies have shown that contractions of (CAG)(95) are more frequent when the repeat tract is transcribed. Here we determined whether transcription can promote repeat expansion, using (CTG)•(CAG) repeat tracts in the size range that is typical for myotonic dystrophy type 1. We deriv
Oral erythromycin treatment, which has been widely used in humans with excellent tolerability, may be a promising therapy for DM1.
Myotonic dystrophy types 1 (DM1) and 2 (DM2) are dominantly inherited neuromuscular disorders caused by a toxic gain of function of expanded CUG and CCUG repeats, respectively. Although both disorders are clinically similar, congenital myotonic dystrophy (CDM), a severe DM form, is found only in DM1. CDM is also characterized by muscle fiber immaturity not observed in adult DM, suggesting specific pathological mechanisms. Here, we revealed upregulation of the interleukin-6 (IL-6) myokine signali
Alternative splicing of alpha-dystrobrevin is dysregulated in myotonic dystrophy type 1 (DM1) muscle, resulting in changes in alpha-syntrophin binding. These results raise the possibility that effects on alpha-dystrobrevin splicing may influence signaling in DM1 muscle cells.
Myotonic dystrophy type1 (DM1) is a multisystemic disorder caused by a CTG repeat expansion in the DMPK gene. Aberrant mRNA splicing of several genes has been reported to contribute to some of the symptoms, including myotonia and insulin resistance, but the cause of muscle wasting is unknown. Dystrophin is a cytoskeletal protein that is required for structural stability and signaling at the sarcolemma and has several spliced isoforms. We investigated the alternative splicing of dystrophin in ske
Muscular dystrophies are a group of diseases that primarily affect striated muscle and are characterized by the progressive loss of muscle strength and integrity. Major forms of muscular dystrophies are caused by the abnormalities of the dystrophin glycoprotein complex (DGC) that plays crucial roles as a structural unit and scaffolds for signaling molecules at the sarcolemma. α-Dystrobrevin is a component of the DGC and directly associates with dystrophin. α-Dystrobrevin also binds to intermedia
Dentatorubral-pallidoluysian atrophy (DRPLA) is a devastating genetic disease presenting myoclonus, epilepsy, ataxia, and dementia. DRPLA is caused by the expansion of a CAG repeat in the ATN1 gene. Aggregation of the polyglutamine-expanded ATN1 protein causes neuro-degeneration of the dentatorubral and pallidoluysian systems. The expanded CAG repeats are unstable, and ongoing repeat expansions contribute to disease onset, progression, and severity. Inducing contractions of expanded repeats can
